In the preceding article, James Davies claims that ‘the largest meta-analysis ever conducted’ by Andrea Cipriani et al. only found a clinically meaningful benefit for a small subset of patients. However, Cipriani et al. themselves reached a different conclusion, reporting that that all 21 antidepressants included in the analysis were more effective than placebos when used to treat major depressive disorder in adults. Although effect sizes were ‘modest’, even small differences might provide the motivation a person requires to, for example, attend therapy or physical exercise sessions, which could result in more significant reduction of depressive symptoms.
Some antidepressants (such as mirtazapine and duloxetine) were also shown to be more effective than others, meaning that it makes little sense to talk of ‘antidepressants’ in general terms. Similarly, many of the problems associated with antidepressants (for example, side effects and withdrawal) vary considerably. For example, agomelatine and fluoxetine as well as new antidepressants (for example, gepirone, approved in 2023) have fewer side effects (for example, weight gain or sexual dysfunction). Furthermore, withdrawal symptoms can be significantly reduced through ‘tapering’ (gradual discontinuation) and exercise, and withdrawal is sometimes associated with positive experiences including weight loss and improvement in recall of positive memories (Mahmood et al. 2024).
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